In numerous medical and veterinary procedures, it is desirable to occlude a tubular anatomical structure such as a blood vessel or a tubular structure in the respiratory, digestive, reproductive or urinary tract of a mammalian subject. These procedures have been performed by surgical intervention as, for example, by making an artificial opening in the body to expose the tubular structure and ligating the tubular structure, by tying a suture around the structure and pulling the suture tight so as to clamp the structure shut. Alternatively, the structure may be cut apart and the open ends may be left in place. The open ends do not reunite with one another, and therefore the structure is occluded. In other procedures, tubular structures have been cauterized by application of heat or other forms of energy within the body. For example, U.S. Pat. No. 5,891,141 discloses an instrument with a set of electrodes which can be inserted through a surgically-created opening in the body to grasp a tubular structure between the electrodes so that radio frequency (xe2x80x9cRFxe2x80x9d) electrical energy can be applied directly to the tissue forming the wall of the structure. Coagulation of the tissue occludes the structure, whereupon the structure is severed by a cutting blade carried on the instrument. Surgical invasion of the body poses at least some risks even if minimally-invasive surgical procedures are employed. Other techniques for occluding anatomical structures include insertion of artificial plugs into such structures as, for example, by threading a catheter or other invasive device into the structure and dispensing a mass of biologically compatible plug material from the tip of the catheter. These techniques require careful selection of the plug material and careful attention to dispensing technique and also require insertion of an instrument into the body.
One example of a procedure which involves occlusion of a tubular anatomical structure is vasectomy, a common male sterilization procedure. A vasectomy is a procedure which occludes or severs the vas deferens so that it cannot serve as a passage for sperm from the testes to the urinary tract. Vasectomies have been performed by surgically opening the scrotum and cutting the vas deferens. Although this is a minor surgical procedure, there is nonetheless some risk associated with it. Also, if the subject later desires to reverse the vasectomy, it is difficult to locate the severed ends to reconnect them with one another. Typically, the ends of the vas deferens retract away from one another with time.
Techniques have been developed for applying hyperthermia to tissue within a living subject by directing energy into the subject from outside the subject""s body. For example, in high intensity focused ultrasound (xe2x80x9cHIFUxe2x80x9d) techniques, ultrasonic energy is applied from a source disposed outside the subject""s body and directed into the subject body in such a manner that the ultrasonic energy comes to a focus at a selected focal point within the body. The focused ultrasonic energy heats the tissue at the focal point. Such techniques have been applied, for example, to ablate unwanted tissues such as tumors, or to potentiate the action of a drug at a particular location within the body. As used in this disclosure, the term xe2x80x9coutside the subject""s bodyxe2x80x9d refers to a location which is either outside of the skin or within the alimentary tract, respiratory tract, or another structure of the body which is naturally open to the outside environment. Thus, a location inside of the mouth or rectum would be considered outside of the body. Because the ultrasonic energy can be applied from outside the body, the ultrasonic hyperthermia procedure can be essentially non-invasive. Techniques of this general type are described in PCT International Publication WO 98/52465, the disclosure of which is incorporated by reference herein. Other techniques for performing hyperthermia utilize radio frequency (xe2x80x9cRFxe2x80x9d) energy instead of ultrasonic energy.
One aspect of the present invention provides methods of occluding a tubular anatomical structure in the body of a mammalian subject. Methods according to this aspect of the invention desirably include the step of directing ultrasonic energy from outside of the subject""s body, into the body and onto the tissue constituting the tubular anatomical structure to thereby kill at least some of such tissue at a location along the length of the anatomical structure, whereby scar tissue will form and occlude the anatomical structure. Desirably, this is accomplished without substantially destroying tissue other than the tissue defining the wall of the tubular anatomical structure. Most preferably, the step of directing ultrasonic energy into the body is performed using a probe having one or more ultrasonic transducers associated therewith and adapted to emit ultrasonic energy so that the ultrasonic energy will be focused in a focal region at known disposition relative to the probe. The probe is positioned and maintained at a preselected disposition relative to a portion of the subject""s body incorporating the tubular anatomical structure so that the focal region encompasses the anatomical structure.
In certain methods according to this aspect of the invention, the probe is positioned relative to the body of the subject without using an image of the internal structures within the body. For example, the step of maintaining the probe in a preselected disposition relative to the portion of the subject""s body containing the tubular anatomical structure may be performed by engaging one or more guide members connected to said probe with such portion of the subject""s body. The guide members desirably include a pair of opposed guide members projecting from the probe so that a portion of the subject""s body, such as a fold of skin containing the tubular anatomical structure is pinched between the opposed guide members. Thus, the tubular anatomical structure is held in registration with the transducer and with the focus of the ultrasonic energy by the guide members.
A further aspect of the invention provides techniques for sterilizing a male mammalian subject, such as a human or non-human mammal. The spermatic ducts of such a subject, including the vas deferens, lie close to the skin of the scrotum. Thus, a portion of the scrotum such as a fold of scrotal tissue containing the vas deferens or other spermatic duct can be engaged with guide members of a probe as discussed above and ultrasonic energy can be directed through the skin of the scrotum covering this fold, onto the spermatic duct, to heat the tissue constituting the wall of the spermatic duct and preferably to kill at least some of this tissue. Scar tissue formed as a result of this procedure effectively occludes the spermatic duct, rendering the subject sterile. The procedure can be performed rapidly, typically in a few minutes or less, and can be performed entirely non-invasively. Further, because the ends of the spermatic duct are not separated from one another, they can be more readily reunited with one another at a later date.
A further aspect of the invention provides apparatus for occluding a tubular anatomical structure. Apparatus according to this aspect of the invention preferably includes a probe including a housing having an operative region and one or more ultrasonic transducers operatively associated with said housing. The transducer or transducers are adapted to deliver ultrasonic energy at a focal region having a known disposition relative to the operative region of the housing. Apparatus according to this aspect of the invention preferably also includes one or more guide members projecting from the housing for engaging a portion of a subject""s body containing the anatomical structure to be occluded so as to hold that portion of the body in position relative to the operative region of the housing so that the focal region will lie at a known disposition relative to the body portion engaged by the guide members. This disposition most desirably is selected so that the focal region encompasses the tubular anatomical structure at one or more points along the length of such structure.
Preferably, the one or more guide members are adapted to engage the skin of the subject""s body covering the engaged portion of the body. The guide members most preferably include first and second opposed guide members adapted to receive a portion of the body between them and to maintain that portion of the subject""s body in preselected disposition relative to the housing of the probe and hence in a preselected disposition relative to the transducer. Most preferably, one or both of the guide members is movable relative to the housing so that said guide members can be moved toward and away from one another so as to pinch a portion of the subject""s body, such as a fold of tissue encompassing the tubular anatomical structure, in a gap between the guide members.
In a particularly preferred arrangement, the guide members are adapted to pinch the portion of the body in a gap between the guide members so that the pinched portion projects generally in a first direction, referred to in this disclosure as the Z direction, relative to the guide members and the probe. The one or more transducers most preferably defines an emitting surface offset in the Z direction from the gap between the guide members, so that the emitting surface will be spaced from the body portion pinched between the guide members. However, the transducer or transducers desirably are arranged relative to the guide members so that the ultrasonic energy will have a focal region or region of maximum intensity extending in the gap between the guide members. The apparatus desirably also includes a flexible sonic transmission element such as a fluid-filled bag extending between the emitting surface and the gap between the guide members so that the flexible sonic transmission element will engage the skin of the pinched portion of the body held in the gap.
In a particularly preferred arrangement, the emitting surface is substantially in the form of a sector of a cylindrical surface having an axis extending in an axial or Y direction transverse to the Z direction. The guide members desirably are movable towards and away from one another generally in an X direction transverse to the axial or Y direction and also transverse to the Z direction. The transducer defines a central or medial plane including the axis of the cylindrical sector and extending through the middle of the sector. The medial plane of the transducer desirably extends substantially in the Y and Z directions, so that the medial plane is transverse to the directions of movement of the guide members, and extends in the gap between the guide members. When a fold of tissue is pinched between the guide members, the medial plane of the transducer is substantially aligned with the medial plane of the fold. As further discussed below, the cylindrical-sector transducer will provide a generally slab-like focal region oriented along the medial plane. The focal region is effectively aligned within the fold of tissue so as to maximize heating within the fold and minimize heating at the skin surface.
In a particularly preferred arrangement, at least one of the guide members includes first and second elements spaced apart from one another, and defining a space therebetween. Desirably, each one of the guide members includes such spaced-apart elements. The fluid bag or other said sonic transmission element most preferably extends into these spaces, so that the transmission element wraps around the fold of tissue. This arrangement provides sonic paths from the transducer into the sides of the fold.
A further aspect of the invention provides methods of performing hyperthermia within the body of a mammalian subject. The method according to this aspect of the invention desirably includes the step of providing an exogenous ultrasonic contrast medium within the body of the subject, i.e., a medium introduced from outside the subject""s body. The contrast medium has sonic propagation properties different than the sonic propagation properties of the tissue surrounding the medium. Most preferably, the contrast medium is a sonically dispersive medium including a fluid and a plurality of micro particles, such as gas-filled micro spheres, having acoustic impedance different from the acoustic impedance of the fluid. The method according to this aspect of the invention most preferably further includes the step of directing ultrasonic energy into the body and focusing the ultrasonic energy in a focal region encompassing at least a portion of the ultrasonic contrast medium. The ultrasonic energy is dissipated and converted to heat preferentially in the medium or at an interface between the medium and the tissue surrounding the medium so as to heat the tissue surrounding the medium. In methods according to this aspect of the invention, the heating effect desirably is substantial, so as to heat the tissue immediately surrounding the medium by at least about 5xc2x0 C., and most desirably so as to heat the tissue by at least about 10xc2x0 C. For example, the ultrasonic energy may heat the tissue surrounding the medium to a degree sufficient to kill at least some of such tissue as, for example, by heating the tissue to a temperature above about 45xc2x0 C., and more preferably above about 60xc2x0 C. The ultrasonic contrast medium may be disposed within a tubular anatomical structure, and the said ultrasonic energy may heat the tissue constituting the wall of the tubular structure at one or more locations along such structure, so that scar tissue will form in the tubular structure and occlude such structure.
These and other features and advantages of the present invention will be more readily apparent from the detailed description of the preferred embodiments set forth below, taken in conjunction with the accompanying drawings.